Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. Uterine leiomyomas are histologically identifiable as benign smooth muscle tumors with varying amounts of associated fibrous tissue. Many women have more than one uterine leiomyoma, but each appears to be clonally distinct. Several specific cytogenetic changes have been identified in tumor tissue, but most show no chromosomal abnormalities. These benign tumors are hormone-dependent. They develop after puberty and regress after menopause. Both estrogen and progesterone are considered important stimulants, or at least permissive factors for tumor growth. To address the research needs in this field we have designed three studies. The first is a large epidemiologic study, the NIEHS Uterine Fibroid Study, designed to 1) estimate the age-specific cumulative incidence of leiomyomas in black and white women, aged 35-49, 2) identify risk factors for the condition, 3) compare growth mediating factors in tumor and matching myometrial tissues collected at time of hysterectomy, and 4) to identify factors associated with development of fibroid symptoms including pelvic pain and uterine bleeding. The second study (Barbara Davis, PI) is a clinical study of fibroids designed to describe fibroid growth and compare the growth-mediating factors in growing vs nongrowing tumors. The third study monitors fibroid change with pregnancy and postpartum uterine regression. Progress Last Year: 1. We have published the primary paper on fibroid incidence in which we estimate that over 80% of blacks and 70% of whites develop fibroids by the time they reach menopause (publication 3). Taking into account fibroid characteristics at time of ultrasound screening had little impact on these estimates (2). 2. We have begun looking at risk factors in black and white participants in the NIEHS Uterine Fibroid Study. Pregnancy appear to have a nonlinear protective relationship which we hypothesize to be related to postpartum uterine regression (1, 4). We have also looked at evidence for viral infection in tumors (8). 3. In two cases we have replicated findings from animal models of fibroids. We find that the location of fibroids is somewhat different for parous and nonpauous women (9), and that prenatal exposure to DES is associated with increased development of fibroids (7). 4. We have begun to look at symptoms of fibroids. Using the data from ultrasound screening, we find that heavy uterine bleeding is greater for women with fibroids, especially large fibroids, but that submucous fibroids (those that abut the endometrium) are not more problematic than intramural (those within the muscle layer) (5). 5. Summary histological measures of the tissue samples from the NIEHS Uterine Fibroid Study are continuing. 6. We continue to enroll women in the Postpartum Uterine Regression Study. 7. The Fibroid Growth Study is continuing. Methods for measuring fibroid growth based on the MRI scans have been developed, and we are beginning to investigate biological markers of growth.